Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 12, 2024

N 6 -methyladenosine (m A) is a chemical modification of RNA and has become widely discussed topic among scientific researchers in recent years. It distributed various organisms, including eukaryotes bacteria. been found that m A composed writers, erasers readers involved biological functions such as splicing, transport translation RNA. The balance the human immune microenvironment important for health abnormalities. Increasing studies have affects development diseases inflammatory enteritis systemic lupus erythematosus (SLE) by participating homeostatic regulation vivo . In this manuscript, we introduce composition, function, its progression diseases, providing new targets directions treatment clinical practice.

Язык: Английский

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The role of genetic diversity, epigenetic regulation, and sex-based differences in HIV cure research: a comprehensive review

Epigenetics & Chromatin, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 3, 2025

Язык: Английский

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Dodging the Host Interferon-Stimulated Gene Mediated Innate Immunity by HIV-1: A Brief Update on Intrinsic Mechanisms and Counter-Mechanisms

Frontiers in Immunology, Год журнала: 2021, Номер 12

Опубликована: Июль 29, 2021

Host restriction factors affect different phases of a viral life cycle, contributing to innate immunity as the first line defense against viruses, including HIV-1. These are constitutively expressed, but triggered upon infection by interferons. Both pre-integration and post-integration events HIV-1 cycle appear play distinct roles in induction interferon-stimulated genes (ISGs), many which encode antiviral factors. However, counteracts mechanisms mediated these through its encoded components. Here, we review recent findings pathways that lead ISGs, employed such IFITMs, APOBEC3s, MX2, ISG15 preventing replication. We also reflect on current understanding counter-mechanisms evade immune responses overcome host Overall, this mini-review provides insights into HIV-1-host cross talk bridging between intracellular research avenues field therapeutic interventions

Язык: Английский

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Retroviral PBS-segment sequence and structure: Orchestrating early and late replication events

Retrovirology, Год журнала: 2024, Номер 21(1)

Опубликована: Июнь 17, 2024

Abstract An essential regulatory hub for retroviral replication events, the 5’ untranslated region (UTR) encodes an ensemble of cis-acting elements that overlap in a logical manner to carry out divergent RNA activities cells and virions. The primer binding site (PBS) activation sequence initiate reverse transcription process virions, yet with structural regulate expression complex viral proteome. PBS-segment also encompasses attachment Integrase cut paste 3’ long terminal repeat into host chromosome form provirus purine residues necessary execute precise stoichiometry genome-length transcripts spliced RNAs. Recent genetic mapping, cofactor affinity experiments, NMR SAXS have elucidated HIV-1 folds three-way junction structure. structure is recognized by host’s nuclear helicase A/DHX9 (RHA). RHA tethers trimethyl guanosine synthase 1 Rev/Rev responsive element (RRE)-containing RNAs m7-guanosine Cap hyper methylation bolsters virion infectivity significantly. trimethylated (TMG) licenses specialized translation proteins under conditions repress proteins. Clearly host-adaption shapeshifting comprise fundamental basis orchestrating both modification m7G-Cap biphasic These recent observations, which exposed even greater complexity biology than previously established, are impetus this article. Basic research fully comprehend marriage structures early late events likely expose immutable virus-specific therapeutic target attenuate retrovirus proliferation. Graphical abstract

Язык: Английский

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Single-base m6A epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4+ T cells

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract N 6 -methyladenosine (m A) is the most prevalent cellular mRNA modification and plays a critical role in regulating RNA stability, localization, gene expression. m A vital modulating expression of viral genes during HIV-1 infection. infection increases levels many cell types, which facilitates replication infectivity target cells. However, function primary CD4 + T cells remains unclear. Here, we demonstrate that Jurkat promotes interaction between writer complex subunits methyltransferase-like 3 14 (METTL3/METTL14). Using single-base A-specific sequencing, identified several differentially A-modified mRNAs, including perilipin ( PLIN3 ), Interestingly, increased level by enhancing its but protein was decreased. Knocking down reduced production enhanced virion infectivity. In contrast, cells, were unaffected infection, knocking out did not impact or These results indicate interplay cell-type specific only observed Overall, our highlight importance HIV-1-infected suggest significance as regulatory mechanism Author Summary common chemical on helps control important for this study, found two proteins, METTL3 METTL14, are responsible adding modifications to RNA. mRNAs with altered one called . stabilized levels, When knocked it decreased made particles more infectious. line, affect knockout alter infectivity, suggesting effect Our findings show host like unique infected

Язык: Английский

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